Ideally, the layout of a manufacturing facility should promote efficient flow of work and people as well as facilitating production control to minimize defects and ensure desired quality in the products manufactured. This is particularly important for the pharmaceutical manufacturing industry which operates under a strict regulatory environment. For example, in the United States, the pharmaceutical manufacturing industry must comply with “Current Good Manufacturing Practices” (CGMP) promulgated by the Food and Drug Administration (FDA). See 21 CFR §§ 210-226. Other regulations or guidelines which the pharmaceutical industry may be subjected to include, for example, World Health Organization GMP guidelines and Pharmaceutical Inspection Co-operation Scheme (PICS). CGMP defines requirements with which a drug manufacturing facility and process must comply. This includes for example, design and construction of building and facility, identifying phase of process, identifying and verifying cleaning and maintenance of equipment, location of equipment, and PICS. See Subpart C 211.42, Subpart D 211.63, Subpart F 211.182, and PICS Chapter 3.4 and 3.5.
Non-conformity with CGMP renders a drug “adulterated” under the Food, Drug and Cosmetics Act. See 21 USC § 501(a)(2)(B) (a drug is deemed adulterated “if the methods used in, or the facilities or the controls used for its manufacture, process, packing or holding do not conform to or are not operated or administered in conformity with CGMP.” The purpose of 21 USC § 501(a)(2)(B) is to protect the public interest, ensuring that that drugs marketed meet the health and safety requirements as well as to satisfy quality and purity characteristics which are claimed to possess. To prevent a drug product from being deemed adulterated, a total quality control, approach and system is necessary. A failure to comply with any regulations may result in the drug being withdrawn from the market, as well as subjecting the manufacturer to sanction. This places a heavy burden on the manufacturer to ensure compliance with CGMP.
However, ambiguity in the language of the statute subjects it to interpretation and imparts uncertainty about the requirements for compliance. For example, compliance is not ensured even though the quality manufacturing process or engineering facility is considered “average” compared to the industry. This is because compliance with the regulations requires that a pharmaceutical product must be manufactured by current good manufacturing practice methods, controls and system in order to protect the public. The absence of a consistent and widely accepted interpretation of some of regulatory requirements has led to increased cost in engineering new facilities. This has also led to longer lead-times and, in some cases, delays in bringing new pharmaceutical products to market. In an attempt to clarify the regulatory requirements, the International Society for Pharmaceutical Engineering and the FDA have cooperated to publish a Baselines Pharmaceutical Engineering Guide (Guide).
The Guide includes suggestions from the FDA for compliance with CGMP. The main basic philosophy promoted by the Guide is “Good Engineering Practice” (GEP), which is defined as “established engineering methods and standards that are applied throughout the project life cycle deliver appropriate, cost effective solutions”. It takes into account the design and installation of facilities and equipment and takes “full account of CGMP, safety, health, environmental, ergonomic, operational, maintenance, recognized industry guidance, and statutory requirements”. See Guide.
FIG. 1 shows a layout of a conventional pharmaceutical manufacturing flicility 101. As shown, the facility comprises a rectangular shaped building with two levels 103a and 103b. Typically, the production area 140 is located on the ground level 103a while non-production areas are located on die second level 103b. Also located on the ground level are storage area 195; and packing area 197. Additional areas, such as changing area 194, cafeteria 191, engineering area 193 can also be included on the ground level. The non-production areas on the second level include administration area 108, laboratory area 141, storage area 145, and HVAC plant room 146. In sonic facilities, all the different areas are provided in a single level.
The various production suites 165 form different stages of a production line for manufacturing pharmaceutical products. Products are tested from the various stages for quality control. The finished products are transferred to the packing area for packaging and then to the storage area.
Although such a layout may comply with CGMP, it is, however, inefficient. For example, quality assurance and quality control cannot be easily and effectively carried out in conventional layouts. The different production stages are not visible from a single point, making it inconvenient to monitor, identify, and verify the manufacturing process. Furthermore, testing of drugs for different stages is inconvenient since the laboratory is not located nearby to provide easy access. These deficiencies increase process time. Therefore, a manufacturer incurs additional costs to ensure that the process can be monitored adequately for verification and quality control, rendering such layouts not cost effective.
From the foregoing discussion, it is desirable to provide a more efficient and cost effective layout for a manufacturing facility.